Sizzle or Fizzle?

[wildthing]

Jan 30, 2017 15:38:43 GMT -5 mango said:

Jan 30, 2017 14:27:27 GMT -5 sophie said:

There is no competition between what MNKD is doing with epinephrine and Primatene. 

Primatene is used as a bronchodilator for asthmatics whereas MNKD's formulation (higher dose) is used for anaphylaxis. 

Corticosteroids have shown to be better for chronic use than a short acting epinephrine inhaler for COPD and asthmatics and albuterol is superior for acute episodes. There isn't much use for Primatene anymore. That's probably why it's not gaining back the popularity it lost.  

• What dosage is MannKind using?

• How do you know it will be a higher dose than what Primatene was?

• Primatene was 0.22mg

• EpiPen is 0.3mg

• EpiPen Jr. is 0.15mg

You really are comparing apples to glow worms here. Sorry. MannKind's Epi tech could be used in the event of a moderate to severe asthma attack if it can treat anaphylaxis. And one would be absolutely stupid to not do so. The POS albutetol inhalers out there will do nothing but land you in the hospital. I have a feeling MannKind's inhaled Epi could come in different dosage formulas. Voila!

Not gaining back the popularity? Seriously? Disinfo, misinfo, all kinds of screwedthefuckupinfo. 

Amphastar's Primatene Mist Advocates Facebook page has over 16,000 followers. How many more people need to follow it to meet your standard of "popular"

Absolutely ridiculous, ignorant and ludicrous to even suggest that just because MannKind's Epi formulation will be a "higher dose" that it cannot be used for asthma. Jesus take the wheel.

I think you're being a little unrealistic considering an asthma treatment. Albuterol inhalers and their kin have been used safely and successfully for many years. They are preferred because they are receptor specific and have fewer side effects than epinephrine. To compete with them would require extensive trials demonstrating not only safety, but superiority as well. It would be another afrezza type situation.  

[therealcd]

Um. Love ya akemp? left for dead as the shorties see it. We'll see.

[mango]

Jan 30, 2017 21:39:54 GMT -5 wildthing said:

Jan 30, 2017 15:38:43 GMT -5 mango said:

• What dosage is MannKind using?

• How do you know it will be a higher dose than what Primatene was?

• Primatene was 0.22mg

• EpiPen is 0.3mg

• EpiPen Jr. is 0.15mg

You really are comparing apples to glow worms here. Sorry. MannKind's Epi tech could be used in the event of a moderate to severe asthma attack if it can treat anaphylaxis. And one would be absolutely stupid to not do so. The POS albutetol inhalers out there will do nothing but land you in the hospital. I have a feeling MannKind's inhaled Epi could come in different dosage formulas. Voila!

Not gaining back the popularity? Seriously? Disinfo, misinfo, all kinds of screwedthefuckupinfo. 

Amphastar's Primatene Mist Advocates Facebook page has over 16,000 followers. How many more people need to follow it to meet your standard of "popular"

Absolutely ridiculous, ignorant and ludicrous to even suggest that just because MannKind's Epi formulation will be a "higher dose" that it cannot be used for asthma. Jesus take the wheel.

I think you're being a little unrealistic considering an asthma treatment. Albuterol inhalers and their kin have been used safely and successfully for many years. They are preferred because they are receptor specific and have fewer side effects than epinephrine. To compete with them would require extensive trials demonstrating not only safety, but superiority as well. It would be another afrezza type situation.  

• Albuterol causes an exhausting list of frequent and common side effects. 

1. More common

* Fast, irregular, pounding, or racing heartbeat or pulse
* shakiness in the legs, arms, hands, or feet
* trembling or shaking of the hands or feet


2. Less common

* Abdominal or stomach pain
bladder pain
* bloody or cloudy urine
* chest discomfort
* chest pain
* cough or hoarseness
* cough producing mucus
* diarrhea
* difficult or labored breathing
* difficulty with swallowing
* dizziness
* feeling of warmth
* fever or chills
* frequent urge to urinate
* hives, itching, or skin rash
* loss of appetite
* lower back or side pain
* nausea
* puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
* redness of the face, neck, arms, and occasionally, upper chest
* runny nose
* sore throat
* swollen, painful, or tender lymph glands in the neck, armpit, or groin
* tightness in the chest
* unusual tiredness or weakness
* weakness

3 Rare

* Hives or welts
* large, hive-like swelling on the face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs
* noisy breathing
* redness of the skin
* swelling of the mouth or throat
* trouble breathing

4. Incidence not Known

* Agitation
* arm, back, or jaw pain
* chest tightness or heaviness
* confusion
* convulsions
* decreased urine
* dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
* drowsiness
* dry mouth
* extra heartbeats
* fainting
* flushed, dry skin
* fruit-like breath odor
* hallucinations
* headache
* increased hunger
* increased thirst
* increased urination
* irritability
* lightheadedness
* muscle pain or cramps
* nervousness
* nightmares
* numbness or tingling in the hands, feet, or lips
* pounding in the ears
* rapid, deep breathing
* restlessness
* shakiness
* slow or fast heartbeat
* stomach cramps
* sweating
* unexplained weight loss
* unusual feeling of excitement
* vomiting

5. Interactions with Medications

* Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.
* Amineptine
* Amitriptyline
* Amitriptylinoxide
* Amoxapine
* Atomoxetine
* Clomipramine
* Desipramine
* Dibenzepin
* Doxepin
* Imipramine
* Iobenguane I 123
* Levalbuterol
* Lofepramine
* Melitracen
* Nortriptyline
* Opipramol
* Protriptyline
* Tianeptine
* Trimipramine

6. Other Interactions

* Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

7. Other Medical Problems

* The presence of other medical problems may affect the use of this medicine.
* Allergy to milk proteins, history or—Proair® Respiclick® should not be used in patients with this condition.
* Diabetes or
* Heart or blood vessel disease or
* Heart rhythm problems (eg, arrhythmia) or
* Hypertension (high blood pressure) or
* Hyperthyroidism (overactive thyroid) or
* Hypokalemia (low potassium in the blood) or
* Seizures, history of—Use with caution. May make these conditions worse.
* Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

8. Storage

* Store the canister at room temperature, away from heat and direct light. Do not freeze.
* Do not keep this medicine inside a car where it could be exposed to extreme heat or cold.
* Do not poke holes in the canister or throw it into a fire, even if the canister is empty.
* Keep the medicine in the foil pouch until you are ready to use it.
* Store at room temperature, away from heat and direct light. Do not freeze.
* Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.
* Keep out of the reach of children.


9. Precautions While Using This Medicine

* This medicine may cause paradoxical bronchospasm, which means your breathing or wheezing will get worse.
* Paradoxical bronchospasm may be life-threatening.
* Check with your doctor right away if you or your child have coughing, difficulty breathing, shortness of breath, or wheezing after using this medicine.

******************10*****************

* Albuterol may cause serious types of allergic reactions, including anaphylaxis.
* Anaphylaxis can be life-threatening and requires immediate medical attention. Check with your doctor right away if you or your child develop a skin rash, hives, itching, trouble breathing, trouble swallowing, or any swelling of your hands, face, or mouth while you are using this medicine.
* Hypokalemia (low potassium in the blood) may occur while you are using this medicine.
* Check with your doctor right away if you or your child have more than one of the following symptoms: convulsion, decreased urine, dry mouth, increased thirst, irregular heartbeat, loss of appetite, mood changes, muscle pain or cramps, nausea or vomiting, numbness or tingling in the hands, feet, or lips, shortness of breath, or unusual tiredness or weakness.


11. Grand Finale

* Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

1. More common

* Body aches or pain
* congestion
* fever
* runny nose
* tender, swollen glands in the neck
* trouble with swallowing
* voice changes

2. Less common

* Difficult, burning, or painful urination
* earache
* headache, severe and throbbing
* muscle or bone pain
* pain
* redness of the skin
* redness or swelling in the ear
* redness, swelling, or soreness of the tongue
* sneezing
* stuffy nose
* swelling
* tenderness
* trouble in holding or releasing urine
* trouble sleeping
* warmth on the skin

3. Rare

* Sleepiness or unusual drowsiness

4. Incidence not known

* Bad, unusual, or unpleasant (after) taste
* change in taste
* feeling of constant movement of self or surroundings
* gagging
* rough, scratchy sound to voice
* sensation of spinning
* tightness in the throat


12. Other side effects not listed may also occur in some patients.

www.ncbi.nlm.nih.gov/pubmedhealth/PMH0044547/#DDIC603121.side_effects_section



* Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients

— CONCLUSION

* Patients with asthma who are hypoxic and inhale β2 agonists have serious systemic vascular side effects which may be an additional explanation for the association between asthma treatment and sudden death.

 thoraxbeta.bmj.com/content/thoraxjnl/56/7/567.full.pdf

[wildthing]

The thing is that epinephrine activates both the alpha and beta receptors while albuterol activates only beta receptors:

en.wikipedia.org/wiki/Adrenergic_receptor

en.wikipedia.org/wiki/Beta2-adrenergic_agonist.

In other words, epinephrine would have all the same side effects as albuterol plus all the additional side effects due to alpha adrenergic stimulation. In addition, research has already shown that the beta agonists are superior to epinephrine for asthma:

news.medinfo.ufl.edu/articles/from-the-lab/over-the-counter-medicine-not-the-best-option-for-asthma/

Cap that off with the fact that the beta agonists are as deeply entrenched for asthma treatment as humalog and novolog are for diabetes, and you're talking about taking on a near impossible task of getting any market share for a technosphere/epinephrine inhaler for asthma.

[lakon]

Jan 31, 2017 10:39:10 GMT -5 wildthing said:

The thing is that epinephrine activates both the alpha and beta receptors while albuterol activates only beta receptors:

en.wikipedia.org/wiki/Adrenergic_receptor

en.wikipedia.org/wiki/Beta2-adrenergic_agonist.

In other words, epinephrine would have all the same side effects as albuterol plus all the additional side effects due to alpha adrenergic stimulation. In addition, research has already shown that the beta agonists are superior to epinephrine for asthma:

news.medinfo.ufl.edu/articles/from-the-lab/over-the-counter-medicine-not-the-best-option-for-asthma/

Cap that off with the fact that the beta agonists are as deeply entrenched for asthma treatment as humalog and novolog are for diabetes, and you're talking about taking on a near impossible task of getting any market share for a technosphere/epinephrine inhaler for asthma.

wildthing made some interesting points, but overstated the case against an OTC Epinephrine inhaler for asthma.

AMPH has the brand Primatene Mist with the technically challenging part solved by moving from CFC (1.0) to HFA (2.0), but the problem is a Human Factor concern of bringing an OTC product back to market with changes to the familiar usage pattern. Many people just do not read the instructions. Interestingly enough, a Technosphere Epinephrine would not have these Human Factor concerns. With any luck, soon, MNKD will have a formulation for Anaphylaxis. (AMPH has regulatory experience with off-label applications for Heroin overdoses. MNKD has patents and processes for manufacturing varying dosages of an API on Technosphere.) One can certainly argue that a Primatene Technosphere Mist (3.0) would have significant advantages to the CFC/HFA formulations. From a marketing perspective, having a previously successful brand name is a big plus. (MNKD is building the Afrezza brand from scratch, and building a brand is a difficult and time consuming task.)

Also, don't forget that MNKD studied the application of albuterol before taking Afrezza for asthmatics. If MNKD can do Technosphere Epinephrine, they most likely can do Technosphere Albuterol. Just a thought...

en.wikipedia.org/wiki/Epinephrine
en.wikipedia.org/wiki/Salbutamol
ir.amphastar.com/releasedetail.cfm?ReleaseID=1005509

[sophie]

Jan 31, 2017 12:40:27 GMT -5 lakon said:

wildthing made some interesting points, but overstated the case against an OTC Epinephrine inhaler for asthma.

what part was overstated?

[mango]

Jan 31, 2017 10:39:10 GMT -5 wildthing said:

The thing is that epinephrine activates both the alpha and beta receptors while albuterol activates only beta receptors:

en.wikipedia.org/wiki/Adrenergic_receptor

en.wikipedia.org/wiki/Beta2-adrenergic_agonist.

In other words, epinephrine would have all the same side effects as albuterol plus all the additional side effects due to alpha adrenergic stimulation. In addition, research has already shown that the beta agonists are superior to epinephrine for asthma:

news.medinfo.ufl.edu/articles/from-the-lab/over-the-counter-medicine-not-the-best-option-for-asthma/

Cap that off with the fact that the beta agonists are as deeply entrenched for asthma treatment as humalog and novolog are for diabetes, and you're talking about taking on a near impossible task of getting any market share for a technosphere/epinephrine inhaler for asthma.

Primatene Mist was already being used by thousands of people. Inhaled Epinephrine for asthma. Your point is moot. Face it, there are many who prefer inhaled Epinephrine over Albuterol.

Cap that off with the fact that tons of people are allergic to Albuterol! Xopenex? No. Too expensive for an alternative. 

Having an inhaled Epinephrine to relieve symptoms for asthma AND anaphylaxis (systemic) is far more useful than a piece of crap thing that includes outdated technology, poor aerodynamics, inferior formulation, and requires unnecessary patient-inhaler coordination called a present day Albuterol MDI. Which is exactly why you see so many asthmatics having to come to the hospital because their inhalers simply cannot address the issue. Why is that? Because the inhalers suck!  

MannKind inhalers and formulations are vastly superior to all others. 

[lakon]

Jan 31, 2017 12:51:55 GMT -5 sophie said:

Jan 31, 2017 12:40:27 GMT -5 lakon said:

wildthing made some interesting points, but overstated the case against an OTC Epinephrine inhaler for asthma.

what part was overstated?

near impossible task

Counterpoint:  AMPH Primatene Mist is far from impossible, apparently, another CRL from possible, but not near impossible. MNKD Technosphere Epinephrine would likely be much better if they were to cross-license the brand with Primatene Mist. Furthermore, if THEY go down this road together, in addition to a Primatene Technosphere Epi Mist, a Primatene Technosphere Albuterol Mist makes all the sense in the world to cover both options for patients.

[mango]

Jan 31, 2017 10:39:10 GMT -5 wildthing said:

The thing is that epinephrine activates both the alpha and beta receptors while albuterol activates only beta receptors:

en.wikipedia.org/wiki/Adrenergic_receptor

en.wikipedia.org/wiki/Beta2-adrenergic_agonist.

In other words, epinephrine would have all the same side effects as albuterol plus all the additional side effects due to alpha adrenergic stimulation. In addition, research has already shown that the beta agonists are superior to epinephrine for asthma:

news.medinfo.ufl.edu/articles/from-the-lab/over-the-counter-medicine-not-the-best-option-for-asthma/

Cap that off with the fact that the beta agonists are as deeply entrenched for asthma treatment as humalog and novolog are for diabetes, and you're talking about taking on a near impossible task of getting any market share for a technosphere/epinephrine inhaler for asthma.

This is simply not true. 

Ever wonder why Albuterol is prescription only? Take a look at the exhausting list of side effects from a previous post. And, somehow inhaled Epinephrine has been an OTC medication and Albuterol has not. 

[sophie]

Jan 31, 2017 13:10:02 GMT -5 lakon said:

Jan 31, 2017 12:51:55 GMT -5 sophie said:

what part was overstated?

near impossible task

Counterpoint:  AMPH Primatene Mist is far from impossible, apparently, another CRL from possible, but not near impossible. MNKD Technosphere Epinephrine would likely be much better if they were to cross-license the brand with Primatene Mist. Furthermore, if THEY go down this road together, in addition to a Primatene Technosphere Epi Mist, a Primatene Technosphere Albuterol Mist makes all the sense in the world to cover both options for patients.

gotcha. I thought you meant the benefits of albuterol over epinephrine was overstated. 

As time has gone on with my investment, I've learned to start picking the brains of as many doctors as possible to see their perspective on drugs. From the handful I've asked about it, it's their opinion that Primatene Mist is antiquated and doesn't have much place on the market. 

I think it's possible that it could get approved, but I don't think there's too large of a market for it. I have both ProAir and Ventolin and they both were around $50 for out of pocket pricing. It's been a long time since Primatene was on the shelf, but I think it sold for around the $20 range, but obviously wouldn't be covered by insurance if it's OTC. There is a similar tablet on the market called Bronkaid that has ephedrine as the main ingredient. I tried to look up sales numbers for it and didn't have much luck. It looks like most people take it as a stimulant and/or to lose weight instead of for asthma. It's behind the pharmacy counter because it's a controlled substance. It would probably take a lot of marketing dollars to make the general public aware of its existence, and has been said by me, wildthing, mnholdem, and others, it'd be tough to convince patients to buy primatene over an albuterol inhaler with fewer side effects and better results. 

It's just my opinion- and I really feel like I'm correct about this, but everyone is free to believe whatever they wish. I just don't see any opportunity for an OTC epinephrine inhaler. 

I'm not sure there is any benefit to using albuterol with FDKP. There is already an oral tablet of albuterol and it has been shown to be less effective than the inhaler. Putting albuterol in TS would make the particles go into the bloodstream instead of staying locally in the lungs. I'm not sure if that's why the tablets were less effective or not, but it would make sense to try to keep the drug where the targeted receptors are instead of trying to send it systemically first before reaching its target. 


www.ncbi.nlm.nih.gov/pubmed/6648053

[sophie]

Jan 31, 2017 13:37:55 GMT -5 mango said:

This is simply not true. 

Ever wonder why Albuterol is prescription only? Take a look at the exhausting list of side effects from a previous post. And, somehow inhaled Epinephrine has been an OTC medication and Albuterol has not. 

Why is any drug prescription only and not OTC? Drugs in general are not safe and people shouldn't be allowed to self medicate. 

Asthma is not generally a life-threatening condition. And I can already predict you'll try to pick that comment apart, so hopefully I can explain what I mean, although I feel it will be in vain. 

Asthma attacks, while serious, are not like anaphylaxis where someone can die within minutes if they're not treated. You typically have several hours to seek help before reaching a critical condition. The majority of fatal asthma related incidents are due to uncontrolled chronic asthma, not a random spontaneous event. For this reason, epinephrine is a horrible treatment method. Epinephrine is a very short acting drug and should only be used as a last resort if nothing else is available. In essence, it's better than nothing, but not by much. It can keep someone alive longer to seek help, but it will do little to nothing to treat the disease. If an analogy would help, it's probably similar to a tourniquet. A quick fix to prolong life but further intervention will still be required. 

Everything wildthing said was 100% true, except for maybe the near impossibility of it getting approved. I personally don't see a reason why the FDA would grant approval. If you don't want to take my word for it, I'd strongly encourage you to ask a knowledgable physician about their thoughts on the matter. 

I won't continue arguing with you since it hardly ever goes anywhere. I know of what I speak and I don't know why you and others on here get so hostile when people try to help you understand different concepts better. It's not an attack or a bash on the company. I'll leave this with you instead of dancing around and around. Form whatever opinion you want on it. Ask a doc if you wish, but at the very least, consider why a prominent disease like asthma doesn't have more OTC options or why epinephrine- a drug that has been around for well over 100 years doesn't have several companies rushing to make an OTC inhaler for it. If there was a market for it, companies would cater to it. 

[liane]

Jan 31, 2017 14:38:40 GMT -5 sophie said:

Putting albuterol in TS would make the particles go into the bloodstream instead of staying locally in the lungs.

You cannot say that; TS has nothing to do with transporting its adsorbed drug across the alveolar bed. That said, TS potentially could carry more albuterol further in to the lungs. Albuterol targets bronchiole constriction, and for that, mists and other propellants are acceptable.

[liane]

Jan 31, 2017 15:02:21 GMT -5 sophie said:

Asthma is not generally a life-threatening condition.

One of my closest friends in med school died from an asthma attack. Please do not speak of what you do not know!

[pengiep]

Not only can you die from asthma, but as a former asthmatic, I'm pretty sure it is one of the worst ways to die imaginable.

[sophie]

Jan 31, 2017 15:06:17 GMT -5 liane said:

Jan 31, 2017 14:38:40 GMT -5 sophie said:

Putting albuterol in TS would make the particles go into the bloodstream instead of staying locally in the lungs.

You cannot say that; TS has nothing to do with transporting its adsorbed drug across the alveolar bed. That said, TS potentially could carry more albuterol further in to the lungs. Albuterol targets bronchiole constriction, and for that, mists and other propellants are acceptable.

I'm very grateful that you've chosen to engage in the conversation to correct errors, although I am saddened that it's only when it conforms to a certain thesis instead of being consistent across the board. 

It looks like I misunderstood the mechanism of FDKP. Truly, thank you for pointing this out as I knew its dissociation was related to pH, but I thought that pH was to the blood profile, not the bronchial cell lining. In that case, I agree with you that albuterol may have potential...